DNA virus infections in humans are the suspected cause of significant morbidity and mortality from neoplastic diseases. DNA viruses also induce tumors in animals and transform normal cells to immortalized neoplastic cells in tissue culture. Transformed cells frequently have the capacity to produce tumors in animals. During transforming infections, portions of the viral genome become inheritable cellular elements; expression of specific regions of this genome is believed to induce the transformed state. The mechanisms by which transformed cells induce neoplasia are obscure. By studying the tumor-inducing capacity, the virus-specific antigenicity and the expression of susceptibility or resistance to lysis by cellular immune effector cells of lines of hamster cells transformed by adenovirus 2, adenovirus 12, SV40, polyoma virus, bovine papilloma virus and BK virus, we have developed a perception that, hopefully, reflects a basic feature of the conversion of normal cells to cells that produce tumors in animals. We are proposing that, during transformation, the virus conveys a specific level of susceptibility or resistance to immune rejection to the immortalized cell. The expression of this susceptible-resistant phenotype determines the success or failure of the cellular immune system of the potential host in eliminating the putatively neoplastic cell. Transformed cells that are susceptible to lysis by the immune defenses of the host will be eliminated, while transformed cells that are resistant to those defenses will present as clinically apparent neoplasias. The expression of the susceptible-resistant phenotype of transformed cells is an event that is independent of transformation per se and of the expression of the cell's virus-specific antigenicity. The reflection of the susceptible-resistant phenotype can be detected by in vitro assays and this parameter possibly represents the first in vitro assayable biologic feature of transformed cells that can be correlated with their tumor-inducing capacity. Using these concepts, we hope to be able to associate the induction of the transformed cell's susceptible-resistant phenotype with the expression of viral antigens and the function of viral proteins in transformed cells.